Fibrinolysis Shutdown Correlation with Thromboembolic Events in Severe COVID-19 Infection

Abstract

Background: COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement. The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events.

Study design: Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied. Conventional coagulation assays, d-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure.

Results: Forty-four patients with COVID-19 were included in the analysis. Derangements in coagulation laboratory values, including elevated d-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes. A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p = 0.021). A d-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p = 0.005). Overall, patients with no lysis of clot at 30 minutes and a d-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p = 0.008), and had a hemodialysis rate of 80% compared with 14% (p = 0.004).

Conclusions: Fibrinolysis shutdown, as evidenced by elevated d-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19. Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.

Graphical abstract

Figure 1

(A) Area under the receiver operating characteristic curve (AUC) for venous thromboembolism prediction. (B) AUC for acute renal failure prediction. LY30, clot lysis at 30 minutes; MA, maximum amplitude.

Figure 2

Clot lysis at 30 minutes (LY30) of any value > 0% predicts fewer venous thromboembolic events (VTEs). AUROC, area under the receiver operating characteristic curve.

Figure 3

d-dimer levels and timing of dialysis.

Figure 4

Combination score predicts venous thromboembolic event (VTE) and dialysis risk. LY30, clot lysis at 30 minutes.

eFigure 1

d-dimer decreases in fibrinolysis shutdown. LY30, clot lysis at 30 minutes.